Abstract:
:T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. In the current study, we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T cell numbers in thymus which was effectively improved by co-treatment with DMY. Quantification of signal joint TCR delta excision circles (TRECs) and Vβ TCR spectratyping analysis were employed to determine the thymus function with indicated treatments. The results showed that DEX-impaired thymus output and decreased TCR cell diversity which was ameliorated by co-treatment with DMY. iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of mice treated with or without indicated agents, followed by informatics analysis to identify the correlated signaling pathway. After validated by Western blotting and Real-time PCR, we found that PPARγ-associated fatty acid metabolism was increased in the thymic tissues of the animals treated with DMY plus DEX than the animals treated with DEX alone. The agonist and antagonist of PPARγ were further employed to verify the role of PPARγ in the present study. Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX on suppressing inflammation in vivo. Collectively, DMY relieved thymus function damaged by DEX via regulation of PPARγ-associated fatty acid metabolism. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate adjuvant natural agents through up-regulation of PPARγ-associated fatty acid metabolism.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Li T,Yan F,Meng X,Wang J,Ting Kam RK,Zeng X,Liu Z,Zhou H,Yang F,Ren R,Liao K,Liu Ldoi
10.1016/j.phrs.2018.09.011subject
Has Abstractpub_date
2018-11-01 00:00:00pages
76-88eissn
1043-6618issn
1096-1186pii
S1043-6618(18)31131-9journal_volume
137pub_type
杂志文章abstract::Radiotherapy plays a critical role in the treatment of non-small cell lung cancer (NSCLC). However, radioresistance is a major barrier against increasing the efficiency of radiotherapy for NSCLC. To understand the mechanisms underlying NSCLC radioresistance, we previously focused on the potential involvement of PIM1, ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2013.01.005
更新日期:2013-04-01 00:00:00
abstract:CONTEXT:Ticagrelor was related to bradycardia in DISPERSE-II trial. This risk has been integrated into the European risk-management plan, and its use is warned in at-risk patients. Nevertheless, this risk was not systematically assessed nor measured. OBJECTIVES:To estimate the risk of bradyarrhythmia associated with t...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105089
更新日期:2020-10-01 00:00:00
abstract::Heparin-binding protein (HBP; CAP37/azurocidin) is secreted from neutrophil leukocytes early during inflammation and plays a central role in early capillary leakage and extravasation of neutrophils. Furthermore, HBP is chemotactic towards monocytes and lymphocytes and protects against stress-induced apoptosis, e.g. in...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.01.004
更新日期:2005-06-01 00:00:00
abstract::The Notch pathway represents a highly conserved signaling network with essential roles in regulation of key cellular processes and functions, many of which are critical for development. Accumulating evidence indicates that it is also essential for fibrosis and thus the pathogenesis of chronic fibroproliferative diseas...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.04.010
更新日期:2016-06-01 00:00:00
abstract::Conjugated linoleic acid (CLA) is being sold as a panacea that has the capability of reducing or eliminating cancer, preventing heart disease, improving immune function, and altering body composition to treat obesity or build lean body mass. Unfortunately, there has been very little published human research on CLA. Th...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.2000.0735
更新日期:2000-12-01 00:00:00
abstract::There is evidence that hydrazine, a metabolite of isoniazid, plays an important role in the mechanism of isoniazid-induced hepatotoxicity. Hydrazine has been reported to be metabolised by NADPH cytochrome P-450 reductase (reductase) to reactive and potentially toxic intermediates. The present study was designed, using...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1998.0347
更新日期:1998-09-01 00:00:00
abstract::The neurohormonal factor arginine vasopressin (AVP) produces potent systemic vasoconstriction as well as water retention in the kidneys via the V(1a) and V(2) receptors, respectively. Therefore, AVP may be considered as an aggravating factor of cardiac failure. In the present study, the effects of intravenous (i.v.) i...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043661802002062
更新日期:2002-11-01 00:00:00
abstract::Cytochrome P450-dependent arachidonic acid (AA) metabolism by medullary thick ascending limb of the loop of Henle (mTALH) cells, corneal epithelium and other transporting epithelia, such as those of the intestines, generate metabolites which affect Na(+)-K(+)-ATPase activity, vasomotion and, thereby, organ function. F...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/1043-6618(91)90046-z
更新日期:1991-05-01 00:00:00
abstract::Poorly managed gestational diabetes can lead to severe complications for mother and child including fetal overgrowth, neonatal hypoglycemia and increased autism risk. Use of metformin to control it is relatively new and promising. Yet safety concerns regarding gestational metformin use remain, as its long-term effects...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.11.013
更新日期:2019-02-01 00:00:00
abstract::Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of gene...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104606
更新日期:2020-02-01 00:00:00
abstract::Contrasting results have been reported on the role of rs628031 and rs683369 polymorphisms of SLC22A1 and rs776746 of CYP3A5 on imatinib treatment response in patients with chronic myeloid leukemia (CML). In the present study, we conducted a systematic review and meta-analysis of published studies to estimate the impac...
journal_title:Pharmacological research
pub_type: 杂志文章,meta分析
doi:10.1016/j.phrs.2018.02.005
更新日期:2018-05-01 00:00:00
abstract::Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analog...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2011.08.011
更新日期:2012-01-01 00:00:00
abstract::In the past two decades, significant advances have been made in the etiology of lipid disorders. Concomitantly, the discovery of liporegulatory functions of certain short-chain fatty acids has generated interest in their clinical applications. In particular, butyric acid (BA) and its derivative, 4-phenylbutyric acid (...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.04.002
更新日期:2019-06-01 00:00:00
abstract::Oxaceprol, an established therapeutic agent for osteoarthritis, had no effect on macrophage prostaglandin E2 release in vitro and inhibited carrageenan paw oedema at high doses (18-150 mg/kg p.o.). In the same dose range, oxaceprol was comparable to indomethacin (3 mg/kg p.o.) as an inhibitor of yeast hyperalgaesia an...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1996.0051
更新日期:1996-06-01 00:00:00
abstract::Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60-90%. So far the precise...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.1999.0535
更新日期:1999-10-01 00:00:00
abstract::The pharmacological physiological effects of the endogenous cannabinomimetic (endocannabinoid) anandamide have been well characterized. Another endocannabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2-AG occurs in vertebrate and invertebrate tissues and binds to both cannabinoid receptors (CB1 ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0702
更新日期:2000-10-01 00:00:00
abstract::Sixteen adult hypertensive patients of both sexes, classified as having 'medium' (total lipid profile 240-300 mg dl(-1)), and 'high' (total lipid profile >300 mg dl(-1)) baseline values, underwent serum lipids, lipoproteins and plasma fibrinolytic parameters evaluations after 3 months of cilnidipine treatment. Patient...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0558
更新日期:2000-01-01 00:00:00
abstract::This brief overview is focused on the inherent duality of immune responses: on the one hand they may induce inflammation and precipitate injury, on the other, a number of examples of participation in organ and tissue repair are growing. These processes will be reviewed from the nephrological stand-point. Specifically,...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2008.05.011
更新日期:2008-08-01 00:00:00
abstract::ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax) are under intensive preclinical and clinical investigation as treatments for hematologic and other malignancies. These small molecules mimic pro-death B-cell lymphoma-2 (Bcl-2) Homology 3 (BH3) domain-only proteins. They also bear a structural resemblance to certa...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.01.040
更新日期:2019-04-01 00:00:00
abstract::The effect of chloroquine and other antimalarial drugs on glutamate dehydrogenase activity was studied in liver and renal mitochondria as well as in kidney-cortex tubules of rabbit. In permeabilized mitochondria, with free access of substrates and drugs to glutamate dehydrogenase, 100 microns chloroquine decreased bot...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1996.0108
更新日期:1997-01-01 00:00:00
abstract::Male Swiss Webster mice exhibited antinociception, hypothermia and Straub tail 3h following a 75mg morphine pellet implantation. These signs disappeared by 72h, and the morphine-pelleted mice were indistinguishable from placebo-pelleted ones, although brain morphine concentrations ranged from 200 to 400ng/gm. We previ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2006.09.007
更新日期:2006-12-01 00:00:00
abstract::The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global "pandemic". At present, the efforts of various countries focus on the rapid di...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.104929
更新日期:2020-08-01 00:00:00
abstract::HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2014.06.011
更新日期:2014-10-01 00:00:00
abstract::Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis and arteriolar hypertrophy. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but previous studies have demonstrated that angiotensin II (Ang II), the pri...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2002.0959
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND:We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. METHODS:Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0581
更新日期:2000-02-01 00:00:00
abstract::Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsib...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2018.02.030
更新日期:2018-04-01 00:00:00
abstract::In spite of continuous research in the field of bronchial asthma, still no satisfactory drug is available. Recently a new class of oligopeptide exhibited antiallergic activity by inhibiting the synthesis of IgE antibody. The analogue of ADSDGK (94-335) has shown antiallergic activity in experimental models. The 94-335...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1998.0302
更新日期:1998-05-01 00:00:00
abstract::We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological condi...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1006/phrs.2000.0709
更新日期:2000-10-01 00:00:00
abstract::The pharmacokinetics of doxycycline hydrochloride (DoxHcl) at a dose of 5 mg kg-1 BW was studied after an intravenous (i.v.) bolus and intramuscular (i.m.) injections in non lactating goats. A microbiological assay employing Bacillus subtilis as the test organism was used to measure its concentrations in serum and uri...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2003.10.012
更新日期:2004-05-01 00:00:00
abstract::In the present study, hyperglycaemia was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner. Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect pl...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1996.0057
更新日期:1996-07-01 00:00:00